Among patients with human epidermal growth factor receptor 2 (HER2, IHC 3+ or IHC 2+/ISH+) positive unresectable and/or metastatic gastric or gastroesophageal cancer, Enhertu (trastuzumab deruxtecan) demonstrated statistically significant and clinically meaningful improvement in overall survival when compared to ramucirumab and paclitaxel, according to a press release from Daiichi-Sankyo.
“Enhertu is the first HER2-directed medicine to demonstrate an improvement in overall survival in a randomized phase 3 trial in the second-line metastatic setting of patients with HER2-positive gastric cancer, reinforcing previous findings seen in our other earlier phase gastric cancer trials,” Dr. Ken Takeshita, who is the Global Head of Research and Development for Daiichi Sankyo, said in the release. “With these DESTINY-Gastric04 results, we will work with global regulatory authorities to seek approval in regions where Enhertu is not currently indicated as a second-line option as well as work to secure full approval in regions where Enhertu is conditionally approved.”
The Independent Data Monitoring Committee recommended unblinding the trial based on the superior efficacy of Enhertu at a planned interim analysis. Data from the trial will be presented at an upcoming medical meeting and will be shared with global regulatory authorities, according to the news release.
Glossary:
Overall survival: the length of time from the start of treatment or diagnosis that patients remain alive.
Progression-free survival: the length of time during and after treatment that a patient lives without disease progression.
Objective response rate: the percentage of patients with a complete or partial response to treatment.
Duration of response: the length of time a tumor continues to respond to treatment without progression.
Disease control rate: the percentage of patients who achieve complete response, partial response or stable disease.
Antibody-drug conjugate (ADC): a targeted cancer therapy combining a monoclonal antibody with a cytotoxic drug.
Tetrapeptide-based cleavable linkers: a type of linker in ADCs that releases the cytotoxic drug upon enzymatic cleavage.
HER2 monoclonal antibody: an antibody targeting the HER2 protein, used in HER2-positive cancer treatment.
Regarding safety, the toxicity profile seen in the DESTINY-Gastric04 trial was consistent with the previously established toxicity profile of Enhertu, as per the release.
ENHERTU is approved in more than 65 countries based on three phase 2 trials: the randomized DESTINY-Gastric01, the single-arm DESTINY-Gastric02 and DESTINY-Gastric06. DESTINY-Gastric04 is the first phase 3 trial evaluating ENHERTU in HER2-positive advanced gastric cancer, as per the release.
“We are committed to advancing the care of patients with metastatic gastric cancer and continuing to understand the role of Enhertu in earlier lines of treatment,” Susan Galbraith, Executive Vice President, Oncology Hematology R&D of AstraZeneca, said in the news release. “The results of DESTINY-Gastric04 show that second-line treatment with Enhertu can extend survival compared with a chemotherapy-based regimen and should be considered for all eligible patients with HER2 positive metastatic gastric cancer.”
Enhertu is a HER2-directed antibody-drug conjugate (ADC). Enhertu consists of a HER2 monoclonal antibody linked to multiple topoisomerase 1 inhibitor payloads, including the exatecan derivative DXd, via tetrapeptide-based cleavable linkers.
DESTINY-Gastric04 is a global phase 3, randomized, open-label trial assessing Enhertu (6.4 milligrams per kilogram) compared with ramucirumab and paclitaxel in patients with HER2-positive (IHC 3+ or IHC 2+/ISH+) unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma that progressed following trastuzumab-based treatment.
The primary endpoint is overall survival, with secondary endpoints including progression-free survival, objective response rate, duration of response, disease control rate and safety. The study enrolled 494 patients across Asia, Europe and South America.
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